Language：English   Publishing type：Research paper (scientific journal)  

On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography-mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 μL of whole blood from dosed rats within ∼10 min. This approach with the 'reusable' sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

DOI： 10.1016/j.heliyon.2023.e15963

PubMed

researchmap

Language：Japanese   Publisher：Japanese Pharmacological Society  

Measurement of plasma drug concentrations at a clinical site is essential for personalized medicine. For such purpose, the conventional liquid chromatography-mass spectrometry (LC-MS) method is unlikely to be suitable, owing to time and cost consumption. In this study, we describe an approach to rapid, easy, and low-cost drug monitoring with a boron-doped diamond (BDD) electrode, an advanced electrochemical material. As a test drug, we selected pazopanib, an inhibitor for multiple tyrosine kinase types. A small size sensor system with a simple BDD plate electrode of ~26 mm² without any chemical modifications determined the drug concentration in a measurement time of ~35 s from 100 µL rat plasma, which was exogenously mixed with pazopanib. We showed that this system was also applicable to blood samples collected from healthy rats orally administrated with pazopanib as well as drug-treated patients with different cancer types. Notably, all the procedures, including sample preparation and electrochemical measurement, were completed in a short time of ~10 min. The pharmacokinetics data obtained by the BDD electrode were similar to the data determined by LC-MS. Finally, we fabricated a prototype of a palm-sized system, which successfully analyzed ~60 µL of rat blood. This strategy may contribute to advances in on-site drug monitoring.

Based on them, we evaluated plasma samples from five rats orally administered pazopanib and eight clinical patients treated with the drug at our institution. The plasma concentrations and other pharmacokinetic parameters obtained by the BDD method were generally consistent with the LC-MS.

Because this strategy by the BDD sensor is more compact and inexpensive than the LC-MS setup, the electrochemical approach described here can be commonly used and contribute to tailor-made medicine.

DOI： 10.1254/jpssuppl.95.0_2-yia-58

researchmap

Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

Molecular-targeted anticancer drugs elicit less toxicity than conventional reagents. Yet, patients often suffer from severe adverse effects. The reason is "fixed dosage" administration of the drug to all the patients regardless of their body size and complications; because of this strategy, the plasma concentration seems to occasionally exceed the therapeutic window. Although frequent measurement of the drug level at a clinical site is a solution, currently available methods are unsuitable. To overcome this shortcoming, in this study we developed a procedure with an electrochemical sensor composed of conductive diamond, which yields more stable reactions than conventional materials. When guinea-pig plasma mixed with imatinib, lenvatinib, or pazopanib were tested, the sensor detected a clinically relevant concentration. Time and sample amount necessary for each series of the measurement was <1 min and 100 μL, respectively. This method may enable therapeutic drug monitoring of molecular-targeted drugs and accelerate tailored medicine for cancer.

DOI： 10.11239/jsmbe.annual58.286

CiNii Article

researchmap

Language：Japanese   Publisher：Japanese Pharmacological Society  

Vancomycin is a glycopeptide antibiotic that kills bacteria by blocking the construction of the cell wall and used to treat different bacterial diseases including meningitis and methicillin‐resistant <i>Staphylococcus aureus</i> infections. Because this antibiotic can sometimes induce renal failure and hearing loss, the plasma concentration is monitored to adjust the dose applied to individual patients. In this study, we show a rapid and simple procedure with an electrochemical approach. The sensor we used consisted of a boron-doped diamond electrode, which elicits more stable reaction than classical materials such as carbon and gold. With this sensor we examined guinea-pig plasma containing vancomycin at different concentrations. The procedure we developed allowed us to complete a series of measurement in 35 sec. Time necessary for all the processes including a sample's pretreatment did not exceed 10 min. The sensor detected the drug concentration of 1 to 50 µM, which falls into the range of the therapeutic window. Moreover, we found that the sensor was repeatedly usable for the measurement with minimal impairment of the sensitivity. The methodology described here may contribute to not only advances in personalized medicine but also reduction of the cost for therapeutic drug monitoring.

DOI： 10.1254/jpssuppl.93.0_1-p-133

CiNii Article

researchmap

Other Link： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16442/

Language：Japanese   Publisher：Japanese Pharmacological Society  

Molecular-targeted anticancer drugs elicit less toxicity than conventional reagents. Yet, patients often suffer from severe adverse effects. A reason is 'fixed dosage' administration of the drug to all the patients regardless of their body size and complications; because of this strategy, the plasma concentration seems to exceed the therapeutic window occasionally. Although frequent measurement of the drug level at a clinical site is a solution, currently available methods such as mass spectrometry are time and cost consuming. To overcome these shortcomings, in this study, we developed a procedure with an electrochemical sensor composed of a conductive diamond, which yields more stable reactions than conventional materials. When guinea-pig plasma mixed with pazopanib, a multi-kinase inhibitor, was tested, the sensor detected a clinically relevant concentration of 3 to 300 µM. Time and sample amount necessary for each series of the measurement was &lt;1 min and 100 µL, respectively. The sensor was repeatedly usable with minimal impairment of the sensitivity, saving the cost for the assay. This rapid and easily-handed method may enable therapeutic drug monitoring and accelerate tailored medicine for cancer.

DOI： 10.1254/jpssuppl.93.0_1-yia-18

CiNii Article

researchmap

Other Link： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16442/

researchmap

researchmap